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Title:	In vitro drug delivery based on a porous membrane-based aqueous-organic partitioning system and its enhancements through mouse skin
Author:	Fan, Qiuxi
View Online:	njit-etd2005-026 (xviii, 93 pages ~ 6.4 MB pdf)
Department:	Committee for the Interdisciplinary Program in Materials Science and Engineering
Degree:	Doctor of Philosophy
Program:	Materials Science and Engineering
Document Type:	Dissertation
Advisory Committee:	Sirkar, Kamalesh K. (Committee co-chair) Michniak, Bozena B. (Committee co-chair) Wu, Jing (Committee co-chair) Chin, Ken K. (Committee member) Kristol, David S. (Committee member)
Date:	2005-01
Keywords:	Drug delivery Aqueous-organic partitioning Enhancements Porous polymeric membrane Mouse skin In vitro
Availability:	Unrestricted
Abstract:	Novel approaches for transdermal drug delivery (TDD) based on a porous membrane-based aqueous-organic partitioning system have been investigated and successful deliveries were observed. Doxycycline hydrochloride (HCl), a polar antibiotic drug with a relatively large molecule weight (MW: 480.1) was studied as a basic model agent. Its controlled release using this technique was studied first. Satisfactory release profiles demonstrate the practical potential of such a system to achieve useful controlled release rates. The enhancer linoleic acid was essential to successful release using a mouse skin beneath a porous polymeric membrane. The transport rates of smaller molecules e.g., caffeine and nicotine from the same system without any enhancer were very high. Iontophoretic TDD was studied next using a porous polymeric conducting membrane of polyaniline (PANi). Doxycycline HCl, lidocaine HCl (MW: 271) and caffeine (MW:194) in their aqueous solutions were model agents. Excellent release profiles were achieved; the conducting PANi membrane appeared to be capable of not only replacing the Ag part of Ag|AgCl electrode system but also providing an additional control over agent transport rate. Aqueous-organic partitioning system was tested with this novel technique as well. Because of the rather low porosity of synthesized PANi membrane, such a system did not yield a high release rate. The transport rates through polymeric membrane alone were accurately predicted using simplified mass transport models for both iontophoretic and non-iontophoretic systems. Finally, a further application of this new technique was investigated using a thermo-sensitive TDD system. A hydrophilic porous PVDF membrane immobilized with a thermo-sensitive polymeric gel, poly(Nisopropylacrylamide) (PNIPAAM)-co-2mol% acrylic acid (AA), demonstrated its release-"on/off' switch function: at normal skin temperature, no release of doxycycline HCl through the skin occurred; under fever condition, certain amount of this antibiotic accumulated beneath the skin.